Diabetic foot ulceration (DFU) and associated impairedhealing, is a major problem that significantly impairs the quality of life of diabetic patients, leading to prolonged hospitalization and resulting to more than 70,000 lower extremity amputations per year in the USA alone. However, there has been very little clinically driven basic research into the molecular mechanisms of the pathophysiology of impaired wound healing in diabetes, hampering the development of effective treatments. The main aim of the current application is to establish collaboration between investigators from bioengineering, basic and translational research that will eventually lead to the development of new biomaterials that will improve DFU healing. To this end, it will involve two investigators from the Wyss Institute and Harvard School of Engineering and Applied Sciences (Drs. Mooney and Shih), with extensive experience on developing new biomaterials and two investigators from the Beth Israel Deaconess Medical Center (Drs. Veves and LoGerfo) with extensive research experience in diabetic wound healing. The new biomaterials that can release substances that studies in the PIs laboratory have shown to improve wound healing, such as neuropeptides, PTP1B inhibitors, growth factors and endothelial progenitor cells, will be constructed will be constructed by the Drs. Mooney and Shih, and will be tested on animal models that have been developed by Drs. Veves' and LoGerfo's laboratory. This collaboratoryoration has the potential to create a unique, highly functional and synergistic investigative team with expertise that cover the whole range of fields that is required for the development of new biomaterials and will exclusively focus in improving diabetic- wound healing. It is our strong belief and hope that this collaboration will lead to the development of new therapeutic approaches for the treatment of DFU that will be clinically available over the next five to ten years. PUBLIC HEALTH RELEVANCE: The current application aims to develop new therapeutic approaches for a major clinical program, namely the management of diabetic foot ulcerations. Successful completion of this project may have a significant impact on the current clinical practice.